Selective Hypothermia in the Management of Traumatic Brain Injury

Eisha Christian, B.A.; Gabriel Zada, M.D.; Gene Sung, M.D.; Steven L. Giannotta, M.D.

Disclosures

Neurosurg Focus. 2008;25(4):E9 

In This Article

Abstract and Introduction

Abstract

Object: Traumatic brain injury (TBI) remains a significant cause of morbidity and death in the US and worldwide. Resuscitative systemic hypothermia following TBI has been established as an effective neuroprotective treatment in multiple studies in animals and humans, although this intervention carries with it a significant risk profile as well. Selective, or preferential, methods of inducing cerebral hypothermia have taken precedence over the past few years in order to minimize systemic adverse effects. In this report, the authors explore the current methods available for inducing selective cerebral hypothermia following TBI and review the literature regarding the results of animal and human trials in which these methods have been implemented.
Methods: A search of the PubMed archive (National Library of Medicine) and the reference lists of all relevant articles was conducted to identify all animal and human studies pertaining to the use of selective brain cooling, selective hypothermia, preferential hypothermia, or regional hypothermia following TBI.
Results: Multiple methods of inducing selective cerebral hypothermia are currently in the experimental phases, including surface cooling, intranasal selective hypothermia, transarterial or transvenous endovascular cooling, extraluminal vascular cooling, and epidural cerebral cooling.
Conclusions: Several methods of conferring preferential neuroprotection via selective hypothermia currently are being tested. Class I prospective clinical trials are required to assess the safety and efficacy of these methods.

Introduction

Traumatic brain injury remains a significant cause of morbidity and death in the US and worldwide. The Centers for Disease Control and Prevention estimates that at least 5.3 million Americans, or ∼ 2% of the US population, currently have a long-term or lifelong need for help to perform activities of daily living as a result of a TBI.[38] Current nonsurgical treatment strategies following TBI consist primarily of ICP management and cardiopulmonary support measures. Although resuscitative hypothermia was initially described as early as 1897[32] and has been established as an effective method of neuroprotection in multiple animal studies,[2,7,16] clinical trials in humans following TBI have been extremely limited until only recently. The multifaceted benefits offered by hypothermic management in achieving neuroprotection, including reductions in the cerebral metabolic rate,[14,22] inflammatory response activity,[40] epileptic discharges,[35] and the production of reactive oxygen species,[26] have supported its role as a potent therapeutic agent in preventing secondary injury associated with TBI.[3]

Results of clinical trials in which authors have implemented systemic hypothermia in humans following TBI have been less definitive, with some studies revealing improved neurological outcomes[15,21,28,31] and others demonstrating more equivocal results.[8,20] Questions regarding patient selection, methods of instituting hypothermia, induction time, depth and extent of hypothermia, and rewarming strategies have been raised as potential factors limiting the observable benefit of this intervention. In many studies, the benefits derived from systemic hypothermia have been offset by appreciable increases in the rates of adverse outcomes.[24] The most frequent risks associated with systemic hypothermia include cardiovascular and pulmonary complications, infections, and increased rates of thrombocytopenia.[8,20,31,34] Additional adverse effects have been associated with the rewarming period following induction of systemic hypothermia and have included severe infections and shock.[25] Given the lack of a clear risk/benefit profile, the Brain Trauma Foundation and the American Association of Neurological Surgeon have issued a Level III recommendation for the optional and cautious use of hypothermia in adults with TBI.[4]

Several investigators have postulated that the administration of selective, or preferential, cerebral hypothermia following TBI may confer the same neuroprotective benefits as systemic hypothermia, while reducing the associated risks. Furthermore, the induction time for selective hypothermia may be shorter, thus providing earlier neuroprotection from secondary injury following TBI. In this report, we examine the currently available methods for implementing selective cerebral hypothermia in patients following TBI and review the literature regarding the results of animal and human trials in which these methods have been applied.

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